High-throughput sample processing systems and methods of use

ABSTRACT

Disclosed herein are high-throughput sample processing systems and waste management systems, and methods of using the same.

FIELD OF THE INVENTION

The present invention relates to the field of sample processing. Morespecifically, the present disclosure relates to high-throughput sampleprocessing systems and waste management systems, and methods of usingthe same.

BACKGROUND OF THE INVENTION

Research or diagnostic laboratories commonly process biological samplesto extract target molecules, such as proteins or DNA, for furtherresearch or diagnostic purposes. Consistent sample processing requirestime-intensive labor from trained technicians or the use of previouslyknown sample processing systems, which have low sample throughput,result in high costs, and risk worker exposure to hazardous waste.

Previously known sample processing systems are limited in the number ofsamples that can be simultaneously processed, provide limitedversatility for extracting different types of target molecules or forintegrating different processing steps, and generate substantial amountsof solid and liquid waste. For example, these previous automatedprocessing systems are often capable of processing a single sampleprocessing plate at a time. Furthermore, these systems require atechnician to remove a processed sample processing plate and insert anew sample processing plate for processing after each completed process.Additionally, previously known automated sample processing systems areoften limited to only DNA extraction or protein extraction throughspecific processing steps, with little ability to quickly exchangeextraction chemistry or alter processing steps to fit the needs of aparticular laboratory. In other words, current systems are notdynamically based on sensed sample input type, e.g., blood, plasma orsaliva.

Previously known automated sample processing systems also producedsubstantial solid or liquid waste, such as used pipette tips or bloodextractions, which must be separately processed or disposed of atsignificant expense, and risks exposing workers to significant hazardouswaste.

SUMMARY OF THE INVENTION

Disclosed are high-throughput sample processing systems, components ofhigh-throughput sample processing systems, sample dispensing devices,contactless fluid dispensing devices, contactless treatment stations,contactless liquid level sensors, contactless fluid aspirators, wastemanagement systems, control systems, and a non-transitorycomputer-readable storage medium for operating a high throughput sampleprocessing system.

In some embodiments, a high throughput sample processing systemcomprises a sample dispensing device, a plurality of contactless liquidlevel sensors, a plurality of aspirators, a plurality of contactlesstreatment stations, a waste management system, and a control system.

In some embodiments, the sample dispensing device can draw a pluralityof samples from a plurality of sample containers and dispense eachsample into a well of a sample processing plate comprising a pluralityof wells. In some embodiments, the sample dispensing device dispenseseach sample into a different well. In some embodiments, the sampledispensing device comprises a plurality of syringe based pipettes. Insome embodiments, the pipettes comprise reusable pipette tips. In someembodiments, the sample dispensing device comprises a washing stationfor automatically washing the reusable pipette tips. In someembodiments, the washing station comprises a bleach solution.

In some embodiments, the contactless fluid dispensing device dispensesfluids into the plurality of wells of the sample processing plate.

In some embodiments, the plurality of contactless liquid level sensorsdetects the liquid level in each of the plurality of wells of the sampleprocessing plate. The liquid level can be determined in a variety ofways, for example, using weight, optical, acoustic, capacitance, or alaser level transmitter. In some embodiments, the liquid level sensorscomprise one or more contactless sensors including one or more acousticsensors, weight sensors, pressure sensors etc. In some embodiments, theliquid level sensors comprise one or more acoustic sensors.

In some embodiments, the plurality of aspirators removes fluids from theplurality of wells of the sample processing plate. In some embodiments,the plurality of contactless treatment stations treats the plurality ofsample processing plates simultaneously.

In some embodiments, the waste management system manages fluids removedfrom the plurality of wells. In some embodiments, the waste managementsystem deposits the fluids removed from the plurality of wells into awaste container. In some embodiments, the waste container operates undera vacuum. In some embodiments, the waste management system mixes thefluids removed from the plurality of wells with a sterilizing solution,e.g., bleach, in the waste container and incubates the mixture. In someembodiments, the waste management system comprises one or more scalesfor determining an amount of fluids removed from the plurality of wells.In some embodiments a variety of sensors may be used to determine theamount of fluids in the waste management system. The sensors mayinclude, for example, acoustic sensors, weight sensors, pressure sensorsetc. In some embodiments, scales are used for determining the amount offluids removed under vacuum. In some embodiments, the amount of fluidtraveling through the system is monitored, for example, to determinewhether there is a leak or error in the system.

In some embodiments, the control system controls the processing of aplurality of plates within the high throughput sample processing systemsimultaneously. In some embodiments, the control system dynamicallycontrols the processing of a plate depending upon the location or statusof other plates in the system.

In some embodiments, the high-throughput sample processing systemcomprises a plate loading device for automatically loading additionalplates into the sample dispensing device.

In some embodiments, the high-throughput sample processing systemprocess a plurality of samples, wherein the plurality of samplescomprise a bodily fluid. In some embodiments the plurality of samplesinclude blood, saliva, or plasma. In some embodiments, the samplecontainers are sealed and the pipettes are configured to draw theplurality of samples through seals of the containers. In someembodiments, the high throughput sample processing system extracts DNAfrom the plurality of samples using magnetic beads.

In some embodiments, the plurality of contactless treatment stationscomprise one or more mixing devices. In some embodiments, the one ormore mixing devices comprises one or more orbital shakers. In someembodiments, the plurality of contactless treatment stations compriseone or more heating or cooling devices.

In some embodiments, the high throughput sample processing systemcomprises a barcode scanner for identifying samples using barcodes onthe sample containers.

In some embodiments, a high throughput sample processing methodcomprises drawing a plurality of samples from a plurality of samplecontainers; dispensing each sample into a well of a sample processingplate comprising a plurality of wells, wherein each sample is dispensedinto a different well; dispensing fluids into the plurality of wells ofthe sample processing plate using a contactless fluid dispensing device;detecting the liquid level in each of the plurality of wells of thesample processing plate using a plurality of contactless liquid levelsensors; mixing a plurality of sample processing plates simultaneouslyusing a plurality of contactless mixing devices; removing fluids fromthe plurality of wells of the sample processing plate using a pluralityof aspirators; and managing fluids removed from the plurality of wellsusing a waste management system.

In some embodiments, a high throughput sample processing methodcomprises dynamically controlling the processing of a plate dependingupon the location or status of other plates. In some embodiments, a highthroughput sample processing method comprises automatically loadingadditional plates into the sample dispensing device.

In some embodiments of a high throughput sample processing method, theplurality of samples comprise blood or saliva. In some embodiments, ahigh throughput sample processing method comprises extraction of DNAfrom the plurality of samples using magnetic beads.

In some embodiments of a high throughput sample processing method, thesamples are dispensed using a plurality of syringe based pipettes. Insome embodiments, the pipettes comprise reusable pipette tips. In someembodiments, a high throughput sample processing method comprisesautomatically washing the reusable pipette tips. In some embodiments,the pipette tips are automatically washed using a bleach solution.

In some embodiments of a high throughput sample processing method, theliquid level sensors comprise one or more acoustic sensors.

In some embodiments of a high throughput sample processing method, thewaste management system deposits the fluids removed from the pluralityof wells into a waste container. In some embodiments, the wastecontainer operates under a vacuum. A series of valves may be included toensure the proper operation of vacuum. In some embodiments the waste isremoved using gravity. In some embodiments, the waste management systemmixes the fluids removed from the plurality of wells with bleach in thewaste container and incubates the mixture. In some embodiments, thewaste management system comprises one or more sensors for determining anamount of fluids removed from the plurality of wells. These sensors mayinclude, for example, acoustic sensors, weight sensors, pressure sensorsetc. In some embodiments, the waste management system comprises one ormore scales for determining an amount of fluids removed from theplurality of wells using a vacuum.

In some embodiments of a high throughput sample processing method, theplurality of contactless mixing devices comprises one or more orbitalshakers.

In some embodiments, a high throughput sample processing methodcomprises scanning with a barcode scanner on the sample containers toidentify the samples.

The system is configured to be dynamic. This means that the system canchange the scheduling and/or control the processing of samples accordingto changing values in the system. These changing values can include, forexample, the location of other sample processing plates in the system,the type of sample, and the type of process being performed (forexample, the type of assay, extraction, and/or treatment).

In some embodiments, a non-transitory computer-readable storage mediumfor operating a high throughput sample processing system comprisesinstructions for dynamically scheduling multiple sample processingplates for processing through a sample processing system, wherein thescheduling depends upon the location or status of other sampleprocessing plates in the sample processing system; controlling one ormore robotic mechanisms for transferring sample processing plates amongdevices within the sample processing system; operating a sampledispensing device operable for drawing a plurality of samples from aplurality of sample containers and for dispensing each sample into awell of a sample processing plate comprising a plurality of wells,wherein each sample is dispensed into a different well; operating acontactless fluid dispensing device operable for dispensing fluids intothe plurality of wells of each of the sample processing plates;operating a plurality of contactless liquid level sensors operable fordetecting the liquid level in each of the plurality of wells of each ofthe sample processing plates; operating a plurality of aspirators forremoving fluids from the plurality of wells of each of the sampleprocessing plates; operating a plurality of contactless mixing devicesfor mixing a plurality of sample processing plates simultaneously; andoperating a waste management system for managing fluids removed from theplurality of wells. In some embodiments, the scheduling depends on asample type, for example blood, saliva, etc. In some embodiments, theinstructions for controlling one or more robotic mechanisms fortransferring sample processing plates among devices within the sampleprocessing system do so according to the dynamic scheduling. In someembodiments, the instructions include dynamic error recoveryinstructions. These instructions may include instructions forcontrolling one or more robotic mechanisms for correcting errors in thesystem. For example, the system may identify and self-address certainissues (e.g., a clot in the pipette tip, insufficient aspiration offluid off of the sample, etc.) before sounding an alarm for humanintervention.

In some embodiments, a waste management system for processing wasteproduced by a high-throughput sample processing system comprises agravity-based liquid waste input, a vacuum-based liquid waste input, asterilizing fluid container, two or more liquid waste containers, andone or more scales for determining the amount of liquid waste collectedby the one or more liquid waste containers. In some embodiments, theliquid waste containers are configured to alternatively accept liquidwaste, treat the liquid waste with a sterilizing fluid, and incubate thesterilizing fluid in the liquid waste for a predetermined period of timebefore disposing of the treated liquid waste.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates one embodiment of a high-throughput sample processingsystem.

FIG. 2 is a flow chart of a method of processing a sample using ahigh-throughput sample processing system.

FIG. 3 illustrates an embodiment of a sample dispensing device.

FIG. 4 is a flow chart of a method of operating a sample dispensingdevice.

FIG. 5 illustrates an embodiment of a contactless fluid dispensingdevice.

FIG. 6 illustrates one embodiment of a high-throughput sample processingsystem with a plurality of contactless treatment stations.

FIG. 7 is a flowchart of a method of a control system dynamicallybalancing parallel processing of a plurality of sample processing plateswhen utilizing a plurality of contactless treatment stations.

FIG. 8 illustrates an embodiment of a contactless liquid level sensor.

FIG. 9 illustrates an embodiment of a contactless fluid aspirator.

FIG. 10 illustrates a waste management system, which may be used in ahigh-throughput sample processing system.

DETAILED DESCRIPTION

Described are high-throughput sample processing systems, and methods ofusing such systems. These systems can be used for conducting assays,purifying and/or isolating compounds, and treating samples. Alsodescribed are components of such high-throughput sample processingsystems, including integrated contactless treatment stations (such asmixing devices and incubation stations), fluid dispensing systems, fluidaeration systems, fluid aspirating systems, liquid level detectionsystems, and waste management systems, as well as methods of using,controlling, and cleaning such systems.

In some embodiments, the high-throughput sample processing systems canbe integrated with other systems, such as assaying, imaging, or finalsample processing systems, to form complete contactless research anddiagnostic laboratory systems. These high-throughput systems are faster,more cost-efficient, and produce less waste than previously knownsystems. Furthermore, the high-throughput systems have a more flexibleworkflow, allowing them to be readily optimized to suit the varyingneeds of a high-throughput sample processing system operator.

In some embodiments, the high-throughput sample processing systems aredesigned to continuously receive and process sample sets such that asecond sample set can begin a process while a first sample set is in anintermediate stage of the same or different process. A control systemcan schedule each sample in the system such that no sample interfereswith any adjacent sample by utilizing parallel work step setups. In thismanner, samples do not need to wait for the preceding sample to completea specified work step.

In some embodiments, the high-throughput sample processing system isfurther designed to minimize solid and liquid waste by utilizingcontactless devices for dispensing, aerating, mixing, and aspiratingfluids. Directly contacting the sample results in contaminatedequipment, which must be properly sterilized or disposed to preventcontamination of the sample. For example, disposal of a pipette tip eachtime a fluid is dispensed, aerated, mixed, or aspirated results insignificant solid waste. Solid and liquid waste can be expensive ordifficult to dispose of because of the presence of biologically activeelements. By minimizing contact with the sample through contactlessdispensing, aerating, mixing, or aspirating of fluids, solid waste andsample contamination can be minimized.

Although contact with the sample is minimized in a high-throughputsample processing system, in some embodiments, contact with the samplemay still be made. For example, in some embodiments, a sample dispensingdevice may transfer a sample from a sample tube to a sample processingplate by withdrawing the sample into a pipette tip or needle anddispensing the sample onto the sample processing plate. Additionally, insome embodiments, fluids aspirated from samples may be contaminated. Ahigh-throughput sample processing system therefore may include a wastemanagement system capable of treating and, in some embodiments,disposing of or containing the waste.

To maintain precision between sample preparations, thereby increasingprocessing reliability, fluids should be consistently dispensed duringsample processing. To ensure consistent fluid dispensing and improveprocessing reliability, some embodiments of the high-throughput sampleprocessing system include a contactless liquid level sensor. Acontactless liquid level sensor can signal to a control system whensufficient fluid has been dispensed into a sample such that the sampleis at a predetermined volume. In some embodiments, the liquid levelsensor detects the sample liquid level without directly contacting thesample. In some embodiments, the liquid level sensor may simultaneouslysignal to the contactless fluid dispensing device when the contactlessfluid dispensing device should continue dispensing fluid and/or when thecontactless fluid dispensing device should stop dispensing fluid.

In some embodiments, each work step in a process may be a distinct stepor event in a complete process, and may use one or more components ofthe high throughput system. For example, in some embodiments, a workstep may be a sample loading step, an incubating step, a mixing step, aheating step, a solution dispensing step, a solution aerating step, or asolution aspirating step. In some embodiments, a work step may includetwo or more simultaneous events, such as simultaneous mixing and heatingsteps, or simultaneous incubating and heating steps. In someembodiments, a work step may include multiple linear or simultaneoussmaller work steps, for example, a cell lysis step may include asolution dispensing step, a simultaneous mixing and heating step, and asolution aspirating step. Other work steps may include, but are notlimited to, a wash step, an imaging step, a weighing step, a dryingstep, a freezing step, a lyophilizing step, or an enzymatic reactionstep.

Any number of fluid solutions may be used in processing a sample in ahigh-throughput sample processing system. For example, a fluid solutionincludes a suspension solution, deionized water, non-deionized water, alysis solution, a wash solution, an elution solution, an assay solution,or a reactive reagent. In some embodiments, the liquid solution maycomprise salts, buffers (e.g., acetate, citrate, bis-tris, carbonate,CAPS, TAPS, bicine, tris, tricine, TAPSO, HEPES, TES, MOPS, PIPES,cacodylate, SSC, MES, succinic acid, or phosphates), amino acids, acids,bases, surfactants, detergents (e.g., SDS, triton X-100, or Tween-20),chaotropic agents, chelators (e.g., ethylenediaminetetraacetic acid,phosphonates, or citric acid), preservatives, antibiotics, alcohols(e.g., methanol, ethanol, propanol, or isopropanol), reducing compounds,oxidizing compounds, dyes, or biomolecules (e.g., nucleic acids,proteins, enzymes (e.g., RNAase or Proteinase K)).

High-Throughput Sample Processing System

In some embodiments, a high-throughput sample processing system includesat least one sample dispensing device, contactless fluid dispensingdevice, contactless liquid level sensor, contactless fluid aspirator,contactless treatment station, waste management system, and controlsystem. In some embodiments, a plurality of identical components of thehigh-throughput sample processing system may be used. In someembodiments, one or more plate loading devices, contactless mixingdevices, contactless heating devices, contactless incubating devices,contactless cooling devices, contactless freezing devices, contactlesslyophilizing devices, weighing devices, or assay or measuring devicesmay be included in the high-throughput sample processing system. In someembodiments, a robotic arm, belt, sled, or drawer may be used totransfer sample processing plates from one station of thehigh-throughput sample processing system to a second station of thehigh-throughput sample processing system.

A high-throughput sample processing system is able to accept a sampleinput and produce a sample output. In some embodiments, ahigh-throughput sample processing system may accept any number of sampleinputs, including, but not limited to, biomolecules, nucleic acid(including DNA or RNA), proteins, peptides, antibodies, antibodyfragments, antibody-small molecule conjugates, enzymes, metabolites,structural proteins, tissues, seeds, cells, organelles, membranes,blood, plasma, saliva, urine, semen, oocytes, skin, hair, feces, cheekswabs, organic molecules, pharmaceutical compounds, bacteria, viruses,or nanoparticles. The output of a high-throughput may be any one of theaforementioned sample input types, in addition to, but not limited to,images, spectroscopy measurements (such as calorimetric, fluorescencemeasurements, light absorbance, nuclear magnetic resonance, infrared,light scattering spectroscopy, etc.), enzymatic measurements (such asdissociation constants, catalytic rates, k_(on) rates, k_(off) rates,etc.), or a target molecule (such as DNA, RNA, protein, peptide, ororganic compound).

In some embodiments, a high-throughput sample processing system can beconfigured to accept a variety of sample containers, for example aplurality of single tubes, a 6-well plate, a 12-well plate, a 24-wellplate, a 48-well plate, a 96-well plate, a 192-well plate, a 384-wellplate, a 1536-well plate, or a multiwell plate capable of holding anynumber of separated samples. In some embodiments, each sample containeris identified with a unique identifier such as a barcode. In someembodiments, the sample containers can be capped or sealed, for exampleby a rubber stopper.

In some embodiments, the high-throughput sample processing system can beconfigured to utilize a variety of sample processing plates, including a6-well plate, a 12-well plate, a 24-well plate, a 48-well plate, a96-well plate, a 192-well plate, a 384-well plate, a 1536-well plate, ora multiwell plate capable of holding any number of separated samples. Insome embodiments, maximum well volume of the sample processing plate maybe about 18 microliters, about 250 microliters, about 1.1 milliliters,about 2.2 milliliters, about 5 milliliters, or about 10 milliliters. Insome embodiments, each sample processing plate is identified with aunique barcode. In some embodiments, the sample processing plate may bepre-loaded with a fluid, such as a lysis fluid, stabilizing fluid, washfluid, deionized water, or ethanol prior to adding a sample.

In some embodiments, each sample well of the sample processing platecomprises affinity beads that can bind to a target molecule within thesample. For example, the affinity beads may be coated in antibodies,streptavidin, or cationic or anionic moieties. In some embodiments, theaffinity beads are magnetic. In some embodiments, affinity beads arepre-loaded into the sample processing plate prior to dispensing of thesample into the sample processing plate. In some embodiments, affinitybeads are not pre-loaded into the sample processing plate.

FIG. 1 provides a schematic of one embodiment of a high-throughputsample processing system 100. Sample containers comprising samplesintended for system processing are placed in the sample containerstation 102. In some embodiments, the sample containers canautomatically be place in the sample container station from storageusing a robotic arm or other automated sample transportation device suchas a belt, sled or drawer. In some embodiments, a sample guard 104 isdisposed directly above the sample container station 102, holding thesample containers in place. In some embodiments, the sample guard 104comprises a plurality of sample ports 106, which are wide enough topermit the passage of a pipette but narrow enough to prevent the passageof a sample container cap or seal. In some embodiments, a sampletransfer device 108 is disposed adjacent to the sample container station102, and comprises a plurality of syringe based pipettes 110. When inoperation, sample transfer device 108 positions the syringe basedpipettes 110 over the sample ports 106, lowers the syringe basedpipettes 110 through the sample ports 106, thereby entering the samplecontainers, and draws a plurality of samples into the syringe basedpipettes 110. In some embodiments, the syringe based pipettes 110pierces the cap or plug of a sample container when being lowered intothe sample containers. The system may then repeatedly draw and ejectliquid from the sample container using the pipettes 110 to mix samplesthat may have settled, for example, blood. Once mixing, if any, iscompleted samples are drawn into the syringe based pipettes 110, thesample transfer device 108 then lifts the syringe based pipettes 110from the sample containers and dispenses samples into a sampleprocessing plate 112 located in a sample processing plate load tray 114.In some embodiments, the sample guard 106 prevents the syringe basedpipettes 110 from removing the cap or plug in the sample containers whenthe syringe based pipettes 110 are removed from the sample containers. Arobotic arm or other transportation device, such as a belt, sled ordrawer, can automatically place the sample processing plates into thesystem from a plate storage area.

In some embodiments, once the sample transfer device 108 has dispensedthe sample into the sample processing plate 112, the syringe basedpipettes 110 are sterilized prior to reuse. The liquid level of a sampledispensed into the plate can be determined by the system, for example,using weight, digital imaging, ultrasonic, capacitance, or a laser leveltransmitter. The liquid level may be adjusted if necessary. In someembodiments, to sterilize the syringe based pipettes 110, the sampletransfer device 108 lowers the syringe based pipettes 110 into a washstation, which comprises a cleaning solution 116, for example a bleach,hydrogen peroxide, iodine, or ethanol solution, and draws the cleaningsolution 116 into the syringe based pipettes 110. In some embodiments,the drawn cleaning solution 116 can continue through a first wasteconduit 118 under vacuum pressure for disposal in a waste managementsystem 120. In other embodiments, the cleaning solution 116 can bedeposited into a waste collection trap connected to the first wasteconduit 118, which flows to the waste management system 120 undergravity forces. Similarly, the syringe based pipettes 110 can be rinsedin deionized water 122, which is drawn into the syringe based pipettes110 and disposed of in the waste management system 120 via the firstwaste conduit 118. Once sterilized and rinsed, the syringe basedpipettes 110 may be reused to draw a new sample.

In some embodiments, once a plurality of samples have been dispensedinto the sample processing plate 112, a robotic arm 124, or otherrobotic transportation device such as a belt, sled, or drawer, canretrieve the sample processing plate 112 and transport it to the nextintended high-throughput processing system 100 component. In someembodiments, once the sample processing plate 112 has been removed fromthe sample processing plate load tray 114, a plate loading device 125automatically loads a new sample processing plate 112 onto the sampleprocessing plate load tray 114.

In some embodiments, the robotic arm 124 or other robotic transportationdevice such as a belt, sled, or drawer, transports the sample processingplate 112 to a sample treatment station 126. In some embodiments, thehigh-throughput sample processing system 100 has one or more sampletreatment stations 126 of the same type or of different types. In someembodiments, the sample treatment station 126 may be heated, chilled, orset to ambient temperature. In some embodiments, a sample treatmentstation 126 may provide contactless mixing of the sample, while in someembodiments a sample treatment station 126 may be stationary. In someembodiments, the sample treatment station 126 may provide both heatingand contactless mixing of the sample. In some embodiments, the sampletreatment station 126 may provide both cooling and contactless mixing ofthe sample. In some embodiments, the sample treatment station 126 may bean orbital shaker, a heating block, or a refrigeration block.

In some embodiments, the robotic arm 124 or other robotic transportationdevice such as a belt, sled, or drawer, transports the sample processingplate 112 to a contactless fluid dispensing device 128. The contactlessfluid dispensing device 128 is disposed to provide a predeterminedamount of fluid into each well of the sample processing plate 112. Insome embodiments, the contactless fluid dispensing device 128 isconfigured to dispense a single type of fluid, while in someembodiments, contactless fluid dispensing device 128 is configured todispense two or more different types of fluids. For example, in someembodiments, the contactless fluid dispensing device 128 is configuredto dispense a high-salt washing fluid 130 and an elution fluid 132. Itis contemplated that the contactless fluid dispensing device 128 can beconfigured to dispense any other type of fluid, for example, but notlimited to, a lysis fluid, an alcohol fluid, a denaturing fluid, anenzymatic fluid, magnetic beads as a slurry, a second wash fluid thatmay be the same or different than the high-salt washing fluid, and/ordeionized water.

In some embodiments, the robotic arm 124 or other robotic transportationdevice such as a belt, sled, or drawer, transports the sample processingplate 112 to a contactless liquid level sensor system 134, whichcomprises a plurality of liquid level sensors 136. The contactlessliquid level sensor system 134 detects the liquid level of each well ofthe sample processing plate 112 and transmits this data to a controlsystem 138.

When the fluid dispensing device is used to dispense a slurry comprisingmagnetic beads a magnetic bead recirculation pump can be used to keepthe beads suspended in the slurry prior to dispensing as the beads cansettle out if they are not continuously stirred. The magnetic beadrecirculation pump preferably does not include any metal contacts thatwould attract the magnetic beads. In some embodiments, a continuousrecirculating pump with a diaphragm pump with all plastic wetted portsis used.

In some embodiments, the robotic arm 124 or other robotic transportationdevice such as a belt, sled, or drawer, transports the sample processingplate 112 to a contactless fluid aspirating system 140, comprising aplurality of contactless fluid aspirators 142. In some embodiments, thecontactless fluid aspirating system 140 is immediately adjacent to thecontactless liquid level sensor system 134 such that the liquid levelsare measured while the sample processing plate 112 is being positionedinto the contactless fluid aspirating system 140. The contactless fluidaspirators 142 use suction forces to simultaneously siphon fluid fromeach sample well in the sample processing plate 112. In someembodiments, the suction force is provided by the waste managementsystem 120, which can also receive aspirated fluid via the second wasteconduit 144. In some embodiments, the suction force is strong enough toaspirate fluid from the sample wells without making contact with thesamples themselves. In some embodiments, the contactless fluidaspirating system 140 lowers the plurality of contactless fluidaspirators 142 into the sample wells at a rate to maintain sufficientsuction force against the sample to aspirate fluid but without causingcontact with the sample.

At the completion of sample processing, the robotic arm 124 or otherrobotic transportation device such as a belt, sled, or drawer, cantransport the sample processing plate 112 to the sample output station146. In some embodiments, once the sample processing plate 112 istransported to the sample output station 146, it may be collected by atechnician. In some embodiments, the processed sample processing platemay be transported directly to an analytical or final processing device148. For example, in some embodiments, an analytical device 148 may bean imager, spectrometer, or scale. In some embodiments, a finalprocessing device 148 may be a heating, freezing, lyophilizing device.

In some embodiments, a high-throughput sample processing system 100comprises a control system 138 for controlling a plurality ofsimultaneously processed sample processing plates 112, receiving barcodedata and liquid level measurements, or system monitoring (includingfluid levels, vacuum pressures, or temperatures). In some embodiments,the control system 138 comprises one or more microprocessors 150 and anon-transitory computer readable storage medium 152. In someembodiments, the control system 138 dynamically schedules multiplesample processing plates 112 depending on the location or status of themultiple sample processing plates 112. In some embodiments, the controlsystem 138 receives multiple sample processing plates 112 location datafrom transmitted barcode readings in the various components of thehigh-throughput sample processing system 100.

In some embodiments, the control system 138 controls one or more roboticmechanisms for transferring sample processing plates 112, for example arobotic arm 124, drawer, sled, or belt. In some embodiments, the controlsystem 138 controls a sample dispensing device 108 to dispense samplesinto a plurality of wells in a sample processing plate 112. In someembodiments, the control system 138 simultaneously controls thetemperature or mixing speed of one or more contactless treatmentstations 126, for example one or more contactless mixing devices,heating devices, or cooling devices. In some embodiments, the controlsystem 138 controls a contactless fluid dispensing device 128 byindicating type and quantity of fluid to be dispensed into the wells ofthe sample processing plate 112. In some embodiments, the control system138 controls a contactless liquid level sensor system 134 and calculatesthe liquid level of a plurality of wells in a sample processing plates112 by receiving data from the contactless liquid level sensor system134. In some embodiments, the control system 138 controls a contactlessfluid aspirating system 140, and in some embodiments the microprocessorcan control return of a sample processing plate 112 to the contactlessfluid aspirating system 140 based on data received from the contactlessliquid level sensor system 134. In some embodiments, the control system138 can control one or more analytical or final processing devices 148.In some embodiments, the control system 138 controls a waste managementsystem 120.

In some embodiments, a non-transitory computer readable storage medium152 comprises instructions for operation of one or more microprocessors150 or control system 138. In some embodiments, the non-transitorycomputer readable storage medium 152 comprises instructions fordynamically scheduling multiple sample processing plates 112 dependingon the location or status of the multiple sample processing plates 112within the high-throughput sample processing system 100.

The control system may also control dynamic error recovery. For example,the system may identify when errors are present in the system andattempt to self-address the issue before sounding an alarm for humanintervention. For example, the system may identify that a clot is in apipette tip and dynamically schedule additional flushing of this pipettetip. The system may also, for example, increase or decrease the amountof fluid delivered or remove/aspirated.

In some embodiments, the non-transitory computer readable storage medium152 comprises instructions for controlling one or more roboticmechanisms for transferring sample processing plates 112, for example arobotic arm 124, drawer, sled, or belt. In some embodiments, thenon-transitory computer readable storage medium 152 comprisesinstructions for controlling a sample dispensing device 108, which candraw samples from a plurality of sample containers and dispense samplesinto a plurality of wells in a sample processing plate 112. In someembodiments, the non-transitory computer readable storage medium 152comprises instructions for controlling a contactless fluid dispensingdevice 128 for dispensing fluid into the wells of the sample processingplate 112. In some embodiments, the non-transitory computer readablestorage medium 150 comprises instructions for controlling a contactlessliquid level sensor system 134, which can detect the liquid level ineach of a plurality of wells in a sample processing plate 112. Theliquid level can be determined by the system, for example, using weight,digital imaging, ultrasonic, or a laser level transmitter. In someembodiments, the non-transitory computer readable storage medium 152comprises instructions for controlling a contactless fluid aspiratingsystem 140. In some embodiments, the non-transitory computer readablestorage medium 152 comprises instructions for controlling a wastemanagement system 120. In some embodiments, the non-transitory computerreadable storage medium 152 comprises instructions for controlling oneor more analytical or final processing devices 148. In some embodiments,the non-transitory computer readable storage medium 152 comprisesinstructions for simultaneously controlling the temperature or mixingspeed of one or more sample treatment stations 126, for example one ormore contactless mixing devices, heating devices, or cooling devices.

FIG. 2 provides a flowchart illustrating one example method 200 of ahigh-throughput sample processing system in operation to process asample. Samples may include a single type of sample or one or moredifferent types of samples including blood, plasma and/or saliva. Thesystem may dynamically control system processing depending upon thesample type(s). At step 210, a technician inputs a plurality of samplesin sample containers into the high-throughput sample processing system.Once the plurality of samples have been inputted into thehigh-throughput sample processing system, the technician need notdisrupt the plurality of samples until the sample outputs are collectedat step 290. Additionally, in some embodiments, the technician may inputmore samples into the high-throughput sample processing system than thesystem is configured to process at any single sample run, as thehigh-throughput sample processing system may be configured tosimultaneously process multiple sample processing plates. For example,in some embodiments, if the high-throughput sample system is configuredto process samples dispensed into a 96-well sample processing plate in asingle sample run, the system may be configured to allow the technicianto load more than 96 samples.

At step 220, a sample dispensing device can simultaneously draw aplurality of samples from the plurality of sample containers anddispense each sample into a plurality of wells in a sample processingplate, such as a multi-well plate, with each separate sample beingdispensed into a separate sample well. Once the plurality of sampleshave been dispensed into the sample processing plate, the sampleprocessing plate can be transported to a contactless fluid dispensingdevice. After the departure of the sample processing plate from thesample dispensing device, in some embodiments, a plate loading devicecan automatically reload the sample dispensing device with a new sampleprocessing plate.

At step 225, a contactless heater can be used to heat the plurality ofsamples to a desired temperature.

At step 230, a contactless fluid dispensing device can dispense apredetermined amount of fluid into the plurality of wells of the sampleprocessing plate. Once the amount of fluid has been added to the sample,the sample processing plate can be transported to the next step of theprocess.

At step 240, the plurality of samples may be treated to any number ofcontactless treatment steps. In some embodiments, the plurality ofsamples undergo one or more of contactless mixing, contactless heating,contactless cooling, or contactless ambient incubation. In someembodiments, contactless mixing is conducted by one or more orbitalshakers. Once the contactless treatment step is completed, the sampleprocessing plate can be transported to a contactless liquid level sensordevice at step 250. In some embodiments, the sample processing plate maybypass the first contactless liquid level sensing step 250 and betransported directly to a contactless aspirating device at step 260.

At step 250, the level of liquid in each well in the sample processingplate can be measured using a plurality of contactless liquid levelsensors in a first contactless liquid level sensing step. In someembodiments, the plurality contactless liquid level sensors can transmitthe liquid level of each sample processing plate well to a controlsystem. In some embodiments, if the liquid level sensor detects a liquidlevel higher than a predetermined level, the control system canterminate system processing or signal an alarm. Once the firstcontactless liquid level sensing step 250 is complete, the sampleprocessing plate can be transported to a contactless fluid aspiratingdevice.

At step 260, a contactless aspirating device can remove fluid from thesample without withdrawing target molecules. In some embodiments, aplurality of contactless aspirating devices are used to aspirate fluidfrom each of a plurality of samples within a sample processing plate. Insome embodiments, such as when magnetic affinity beads are used tocontact target molecules, a magnet can be used to contain targetmolecules at the base of the sample container while the aspiratingdevice pulls liquid from the top of the sample using suction forces. Insome embodiments, the aspirating device does not touch the sample, butsuction forces are strong enough to cause fluid to be pulled into theaspirating device. Aspirated fluid can then be transported to a wastemanagement system using a waste conduit in step 270.

At step 270, the waste management system can treat aspirated fluid fromstep 260 for appropriate liquid waste disposal. In some embodiments, theamount of liquid waste is measured, for example by weighing the liquidwaste collected using a scale. In some embodiments, an amount ofsterilizing solution, for example bleach, is added to the collectedliquid waste to treat the waste. The amount of bleach being dispensedcan be monitored using a sensor, for example an acoustic sensor, toensure the correct volume is dispensed. In some embodiments, the liquidwaste and sterilizing solution mixture is allowed to incubate for apredetermined period of time before it is removed from the wastemanagement system, for example by draining into a sewage system. One ormore fluid flows in the waste management system can be monitored toensure that all waste is accounted for in order to detect errors and/orleaks in the system. These fluid flows can be monitored, for example, bysensors that detect pressure, weight and/or volume of the fluid flows.

In some embodiments, after the completion of the contactless fluidaspirating step 260, a second contactless liquid level sensing step 280allows the plurality of contactless liquid level sensors to determinethe level of liquid in each well of the sample processing plate. Thelevel of the liquid in each sample well may be transmitted to thecontrol system where, in some embodiments, the control system cancompare the level of liquid in each well during the second contactlessliquid level sensing step 280 with the level of the liquid in each wellduring the first contactless liquid level sensing step 250. Aninsufficient difference between the liquid levels during the twocontactless liquid level sensing steps indicates the contactless fluidaspirating device may be acting improperly, and the control system mayterminate sample processing, signal an alarm, or redeploy the sample tothe contactless fluid aspirating device for additional fluid aspirationat step 260.

In some embodiments, after the second contactless liquid level sensingstep 280, the sample may be transported back to the contactless fluiddispensing system at step 230 for iterative processing. In someembodiments, the iterative processing cycle may be performed one or moretimes and can be controlled by a control system. At each iterativecycle, the contactless fluid dispensing system may dispense the same ora different fluid as the previously dispensed fluid. Similarly, at eachiterative cycle, the contactless treatment step 240 may comprise thesame or different contactless treatments. For example, a sample mayfirst be treated with a lysis fluid by a contactless fluid dispensingsystem at step 230 and heated and mixed using a heated contactless mixerat step 240 in a first iteration, followed by the sample being treatedwith a wash fluid at step 230 and cooled and mixed using a chillingcontactless mixer at step 240 in a second iteration. In someembodiments, to ensure proper functioning of the contactless aspiratingdevice and avoid unintentional overfilling of the sample processingplate wells, the liquid level of the sample wells can be determined insteps 250 and 280 during each iteration and transmitted to the controlsystem.

In some embodiments, after the final contactless liquid level sensingstep 280, the sample output is made available in step 290. In someembodiments, the final contactless liquid level sensing step is step 250and not step 280, for example after iterative processing when no furtherfluid aspiration is necessary. In such an embodiment, the sampleprocessing plate can be transported to the sample output at step 290after completion of the contactless liquid level sensing step 250. Insome embodiments, the sample output is made available to a technicianfor collection or further processing. In some embodiments, the sampleoutput is automatically transferred to another robotic station or systemfor further processing. In some embodiments, the further processingincludes freezing, lyophilizing, assaying, and/or imaging. In someembodiments, the samples may be transferred to another tray at amagnetic station to separate the samples from any magnetic beads priorto further processing.

The steps of the high-throughput sample processing system 100 can bedynamically scheduled by a control system to ensure correct processingsequence and coordinating a plurality simultaneously processed sampleprocessing plates. In some embodiments, 1 or more, 2 or more, 3 or more,4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10or more sample processing plates can be simultaneously processed. Insome embodiments, for example, a first sample processing plate mayundergo a contactless mixing at step 240 while a second sampleprocessing plate is receiving fluid from the contactless fluiddispensing system at step 230. In some embodiments, a first sampleprocessing plate may undergo a contactless mixing at step 240 with nofurther iterative processing steps while a second sample processingplate is simultaneously undergoing a contactless mixing at step 240 by aseparate contactless mixer with an additional iterative processing stepbefore the sample is outputted.

In some embodiments, one or more of the sample dispensing systemdevices, the contactless fluid dispensing device, the contactlesstreatment stations, the contactless liquid level sensor system, thecontactless fluid aspirator, or the sample output station comprise abarcode scanner that is configured to read a barcode on a samplecontainer or sample processing plate to assign a location to the samplecontainer or sample processing plate, and transmit this location to thecontrol system. In some embodiments, the control system may then log thelocation, initiated process step, or completed process step of eachsample container or sample processing plate and determine the nextprocess step for each sample or sample processing plate based on itslocation and previously completed process step. The control system istherefore able to balance the steps of each of the simultaneouslyprocessed samples and sample processing plates.

In some embodiments, two or more sample processing plates may besimultaneously processed at the same processing step, although thesample processing plates may be undergoing different iterations of thesame processing step. For example, a first processing plate may beundergoing a contactless treatment step, for example contactless mixing,when a second processing plate is scheduled to initiate a contactlesstreatment step, for example contactless mixing. In some embodiments, acontrol system is able to balance the contactless treatment step bydetermining the location of the first processing plate at a firstcontactless treatment station and controlling a robotic arm, belt, sled,or drawer to transport the second processing plate to a secondcontactless treatment station. The control system can therefore schedulemultiple sample processing plates such that the sample processing plateis transported to a vacant location rather than an occupied location.

By dynamically balancing multiple sample processing plates, ahigh-throughput sample processing system can have significantlyincreased throughput with significantly reduced waste and smaller systemfootprint. In some embodiments, a high-throughput sample processingsystem can process more than about 480 samples per day, more than about960 samples per day, more than about 1440 samples per day, more thanabout 1920 samples per day, more than about 2100 samples per day, ormore than about 2580 samples per day.

Sample Dispensing Device

A sample dispensing device can transfer a plurality of samples from aplurality of sample containers to a plurality of wells of a sampleprocessing plate. The dispensed samples can then continue to beprocessed by the high-throughput sample processing system whileadditional samples are dispensed into a new sample processing plate. Insome embodiments, the sample dispensing device comprises a sampletransfer device, one or more syringe based pipettes (and/or otherdispensing devices such as peristaltic pump, centrifugal pumps,microannuler pumps, etc.), a sample guard, and a wash station. In someembodiments, the sample dispensing device comprises a plate loadingdevice to reload sample processing plates. In some embodiments, thesample dispensing device comprises a barcode scanner.

FIG. 3 illustrates one embodiment of a sample dispensing device 300. Insome embodiments, the inputted samples containers 302 are placed in asample container bay 304. The inputted sample containers compriseseparate tubes, which may be capped or sealed, for example by a rubberstopper 306. In some embodiments, the samples are under vacuum pressurewithin the sample containers. In some embodiments, a barcode 308 isprovided on each sample container 302, which can be scanned by a barcodescanner. In some embodiments, a barcode scanner is configured to scan abarcode on a sample processing plate 310, scan a barcode on a pluralityof sample containers, and assign a sample well location within thesample processing plate 310 to each sample. The barcode can me placedanywhere on the container 302, for example, on the side or bottom of thecontainer 302. A variety of different barcodes may be used including oneand two dimensional barcodes. In some embodiments, the barcode scannertransmits the sample well location of each sample to a control system.This allows the control system to record and monitor the location ofeach sample once dispensed by the sample dispensing device 300 into asample processing plate 310. In some embodiments, the order of samplesin the system may not matter as the sample barcodes are checked againsta database allowing the system to know the type of sample (saliva, bloodplasma etc.), the type of sample assay to run, and the location of thesample in the system.

In some embodiments, a sample dispensing device 300 comprises a sampletransfer device 312 configured with a plurality of syringe basedpipettes 314. In some embodiments, sample transfer device controls apiston, which when drawn allows the syringe based pipettes 314 to draw asample. In some embodiments, the sample transfer device can lower theplurality of syringe based pipettes 314 into the sample containers 302to access a sample. In some embodiments, the syringe based pipettes 314pierce a sample container cap or seal 306 to access the sample. Thesample transfer device 312 can activate the syringe based pipettes 314drawing the sample into the pipette, and subsequently the pipette can beraised out of the sample container 302.

In some embodiments, a sample guard 316 can be placed over the samplecontainers to prevent the sample container cap or seal 306 from beingdislodged while the syringe based pipettes 314 are being raised by thesample transfer device 312. In some embodiments, the sample guard 316has an opening large enough to allow the pipette to pass but not solarge as to allow displacement of the sample container cap or seal 306.In some embodiments, a system operator can readily exchange the sampleguard 316 to accommodate different size sample containers. For example,in some configurations the sample guard 316 is designed to accommodatewide sample containers 302, such as those commonly used for salivacollection, while in other configurations the sample guard is designedto accommodate narrower sample containers 302, such as those commonlyused for blood collection. Easy exchange of the sample guard 316increases the versatility of the high-throughput sample processingsystem, allowing it to accommodate a variety of input sample containers302.

Once the sample transfer device 312 has drawn a sample from a samplecontainer, the sample transfer device 312 can dispense the sample into adefined location within a sample processing plate 310. In someembodiments, the sample processing plate is pre-loaded with a fluid,such as a lysis fluid, stabilizing fluid, wash fluid, deionized water,or ethanol solution prior to adding a sample. In some embodiments, thesample dispensing device may mix the dispensed sample with a pre-loadedfluid, for example by aspirating and redispensing the mixture.

Previous sample processing systems provided for disposable pipettes todispense samples, resulting in significant solid waste. In someembodiments of the high-throughput sample processing system, the syringebased pipettes 314 are reusable. In some embodiments, after the sampletransfer device 312 has dispensed a sample into the sample processingplate the syringe based pipettes 314 are automatically washed at awashing station 318. In some embodiments, a washing station may comprisea cleaning solution 320 and deionized water 322. Preferably, thecleaning solution 320 is a bleach solution, however any solution thatcan clean or sterilize the pipettes may be used, including hydrogenperoxide, iodine, or alcohol solutions. Solutions used for cleaning thesyringe based pipettes pipettes can be disposed of in a waste container324, which is fluidly connected to a the waste management system.

In some embodiments, the sample dispensing device 300 can be configuredto utilize any type of multiwell sample processing plate 310. Once thesample dispensing device has completed dispensing samples on the sampleprocessing plate 310, the loaded sample processing plate can betransported to the next step of processing. In some embodiments, a plateloading device 326 can automatically reload the sample dispensing devicewith a new sample processing plate 310.

FIG. 4 illustrates one example method of operating a sample dispensingdevice. At step 405, a laboratory technician, robotic arm, or otherautomated loading device loads a plurality of sample containers into aninput station of the sample dispensing system. In some embodiments, asample guard may be placed over the plurality of sample containers toprevent displacement of a sample container seal or cap.

At step 410, a barcode scanner scans a barcode on a sample processingplate, scans a barcode on a first sample container amongst a pluralityof sample containers, and assigns the sample to a sample well on thesample processing plate. The sample location is then transmitted to acontrol system.

At step 415, a syringe based pipette is lowered into the samplecontainer, and, in some embodiments, pierces through the samplecontainer cap or seal. In some embodiments, a plurality of syringe basedpipettes are simultaneously lowered into a plurality of samplecontainers.

At step 420, a sample transfer device pulls a syringe plunger in thesyringe, drawing a predetermined amount of sample from the samplecontainer into the pipette. In some embodiments, a plurality of samplesare simultaneously drawn into a plurality of pipettes. In someembodiments, the samples are mixed prior to drawing a sample into thepipette. For example, blood samples may need to be mixed because ofsettling. The samples may be mixed using the pipettes, for example byrepeatedly drawing and ejecting a portion of the sample using thepipettes. In some embodiments, the sample containers are mixed using anorbital shaker or other contactless mixing device. In some embodiments,the drawn sample is about 25 microliters or less, about 50 microlitersor less, about 100 microliters or less, about 150 microliters or less,about 275 microliters or less, about 500 microliters or less, or about1000 microliters or less. In some embodiments, the drawn sample islarger than about 1000 microliters

At step 425, the pipette (or plurality of pipettes) loaded with a sample(or plurality of samples) is lifted out of the sample container. In someembodiments, a sample guard prevents the syringe based pipette fromdislodging a sample container cap or seal.

At step 430, the sample (or plurality of samples) is dispensed into thesample processing plate according to the location assigned in step 410.In some embodiments, for example where the sample processing plate ispre-loaded with a fluid, the sample may be mixed by drawing the sampleback into the pipette and redispensing the sample to the same samplewell location one or more times. In some embodiments, the samples aremixed using an orbital shaker or other contactless mixing device.Following the dispensing of the samples the pipettes may be flushed.

At step 435, the pipettes are lowered into a cleaning solution, forexample a bleach, hydrogen peroxide, iodine, or ethanol solution, andthe cleaning solution is drawn into the pipettes.

At step 440, the cleaning solution is dispensed into a waste receptacle,which is fluidly coupled to a waste management system by a wasteconduit. In some embodiments, a single waste receptacle is used. In someembodiments, the dispensed cleaning solution flows to the wastemanagement system under gravity or suction forces. In some embodiments,steps 435 and 440 are repeated one or more times.

At step 450, the pipette tips are flushed by, for example, drawingdeionized water into the pipettes and then dispensing the fluid into awaste receptacle, which is fluidly coupled to a waste management systemby a waste conduit. In some embodiments, the dispensed deionized waterflows to the waste management system under gravity or suction forces. Insome embodiments, step 450 is repeated one or more times. In someembodiments, after step 450, the sample dispensing device may continueto load additional samples onto the sample processing plate by returningto step 410. If the sample processing plate is fully loaded with samplesor no additional samples are available to be loaded, the sampledispensing device proceeds to step 455.

In some embodiments, at step 455, a robotic arm, belt, sled, or drawermay remove the sample processing plate from the sample dispensingdevice. In some embodiments, the sample processing plate may proceed toa subsequent step in the high-throughput sample processing system, forexample a contactless treatment step, a contactless fluid aspiratingstep, or a contactless fluid dispensing step.

In some embodiments, at step 460, once the sample processing plate isremoved from the sample dispensing device, a plate loading deviceautomatically loads a new sample processing plate into the sampledispensing device.

This process allows a sample dispensing device to transfer samples froma sample container to a sample processing plate while eliminating solidwaste. Furthermore, this process allows a location to be assigned toeach sample so that a control system can monitor sample progressionthrough the system.

Contactless Fluid Dispensing Device

A contactless fluid dispensing device can dispense fluid into aplurality of wells of a sample processing plate during high-throughputsample processing system operation without contacting fluids already inthe wells. In some embodiments, the amount of fluid dispensed iscontrolled by a control system, and may be predetermined or determinedby the control system in response to an earlier liquid leveldetermination. In some embodiments, the contactless fluid dispensingdevice comprises a barcode scanner, which may read a barcode on a sampleprocessing plate and transmit the location of the sample processingplate to the control system. In some embodiments, the bardcode scannermay not be used at this point in the process as once the samples areinitially scanned by the system, the system can determine the locationof each sample without further scanning. The contactless fluiddispensing device can dispense fluids based on, for example, the assayand/or extraction method to be used.

FIG. 5 illustrates one embodiment of a contactless fluid dispensingdevice 500. In some embodiments, the contactless fluid dispensing device500 is configured with one or more fluid dispensing nozzles 502 todispense fluid into the plurality of wells on the sample processingplate 504. In some embodiments, the sample processing plate 504 can bemoved to allow the wells of the plate to be disposed directly underneaththe fluid dispensing nozzles 502, for example by use of a drawer orsled, while in some embodiments, the fluid dispensing nozzles can bemoved to allow the fluid dispensing nozzles 502 to be disposed directlyabove the wells of the sample processing plate 504. In some embodiments,the plurality of wells of the sample processing plate 504 receive fluidsimultaneously, while in some embodiments, the wells of the sampleprocessing plate receive fluid sequentially.

In some embodiments, the contactless fluid dispensing system 500comprises a drainage tray 506 disposed underneath the sample processingplate while fluid is being dispensed, which allows collection of anyfluid which might accidently overflow from the sample wells. In someembodiments, the drainage tray 506 comprises a waste collection groove508 fluidly connected to waste management conduit 510, which leads to awaste management system. Overflowed samples as well as waste frompriming and purging of the dispensing lines, which may includebiohazardous waste, can then be safely disposed by the waste managementsystem without the need for substantial cleanup of the fluid dispensingsystem 500.

In some embodiments, the contactless fluid dispensing system may beconfigured to dispense one or more different types of fluid. In someembodiments, the contactless fluid dispensing system may comprise afluid valve(s) 512. The fluid valves are configured to allow liquid tobe pulled from one or more fluid reservoirs 514 and 516. The fluidreservoirs may include a variety of fluids, for example, washes,reagents, rinses etc. The fluids may be pre-mixed before beingdispensed. The fluid reservoirs may be scalable according to the volumeused in the system and the volume of the source fluid. The scalabilityof these reservoirs helps allow for unattended operation of the systemduring operation.

In some embodiments, a pump 518 can draw fluid from a reservoir 514 or516 to dispense a determined or predetermined amount of fluid into thewells of the sample processing 504 plate via fluidly connected nozzles502. In some embodiments, two or more pumps 518 draw from two or moredifferent reservoirs 514 and 516 and dispense fluid via the nozzles onlyafter the fluid is mixed by a fluid mixer 512. In some embodiments, theproportion of mixed fluids is controlled by the rate at which fluid isdrawn by the separate fluid pumps 518. In some embodiments valves can beincluded in the system to allow a fluid pump 518 to draw and dispenseliquids from multiple fluid reservoirs 514 and 516.

Contactless Treatment Station

Previously known sample processing systems treated or mixed samples byrepeated aspirating and dispensing of the sample with disposable pipettetips or stirring with disposable rods or magnetic stir bars placedwithin the sample. Using these contacting means to treat samples resultsin substantial solid waste, which must be properly disposed of and/ortreated. Some embodiments of a high-throughput sample processing system,as described herein, therefore use one or more contactless treatmentstations to mix or otherwise treat samples. The contactless treatmentstep, such as contactless mixing, does not use magnetic stir bars,disposable rods, or repeated aspiration and solution dispensing to mixthe processing samples. This contactless method of treating samplesresults in significant reduction of waste compared to previously knownsample processing systems.

In some embodiments, the contactless treatment station may comprise acontactless mixer, a water bath, a contactless heater, a contactlesschiller, or a contactless ambient incubator. In some embodiments, thecontactless treatment station may comprise two or more functionalelements, such as heated contactless mixing or chilled contactlessmixing. In some embodiments, the contactless treatment stations comprisea barcode scanner, which can scan a barcode provided by the sampleprocessing plate and transmit the location of an individual sampleprocessing plate to a control system.

In some embodiments, a contactless mixer is an orbital shaker (such as ahigh-speed orbital shaker). In some embodiments, the sample processingplate fits into a nest to secure the plate on the contactless mixer. Insome embodiments, the contactless mixer rotates at about 50 rotationsper minute (rpm) or more, about 250 rpm or more, about 500 rpm or more,about 1000 rpm or more, about 2000 rpm or more, or about 3000 rpm ormore.

In some embodiments, the contactless treatment station can be heatedusing a heating block (such as a dry block heater or a heated waterbath) to a temperature of about 25° C. or more, about 30° C. or more,about 37° C. or more, about 45° C. or more, about 65° C. or more, orabout 95° C. or more. In some embodiments, the contactless treatmentstation can be chilled using a chilling block (such as a dry blockchiller or an ice bath) to a temperature of about 25° C. or less, about20° C. or less, about 15° C. or less, about 5° C. or less, about 0° C.or less, or about −5° C. or less, or about −20° C. or less. In someembodiments, the contactless treatment stations comprise a thermometer,and in some embodiments the contactless treatment stations transmittemperature or rotation speed to the control system.

In some embodiments, the contactless treatment station may provide bothmixing and heating or both mixing and chilling. For example, thecontactless treatment station may be a thermo shaker.

In some embodiments, a high-throughput sample processing systemcomprises one or more contactless treatment stations. In someembodiments, a high-throughput sample processing system comprises two ormore, three or more, or four or more contactless treatment stations. Insome embodiments of a high-throughput sample processing system inoperation, the contactless sample treatment step is a longer step thanother processing steps. For example, in some embodiments, thecontactless sample treatment step is longer than the sample dispensingstep, the contactless fluid dispensing step, the contactless liquidlevel sensing step, or the contactless fluid aspirating step.

To prevent a backlog of sample processing plates, in some embodiments ofthe high-throughput sample processing system, multiple contactlesssample treatment stations are operated in parallel. For example, at someperiods of time during the high-throughput sample processing systemoperation, a first sample processing plate undergoes contactless sampleprocessing at a first contactless sample processing station while asecond sample processing plate undergoes contactless sample processingat a second contactless sample processing station. Also, at some periodsof time during the high-throughput sample processing system operation, afirst sample processing plate undergoes contactless sample processing ata first contactless sample processing station while a second contactlesssample processing station is idle and awaiting the loading of a secondsample processing plate.

FIG. 6 illustrates one embodiment of a high-throughput sample processingsystem 600 with multiple contactless treatment stations. In someembodiments, the high-throughput sample processing system 600 comprisesa sample dispensing device 602, a contactless fluid dispensing device604, a contactless liquid level sensory system 606, a contactless fluidaspirator 608, a robotic arm 610, an output station 612, and a pluralityof contactless treatment stations 614, 616, 618, 620, 622, and 624. Insome embodiments, the plurality of contactless treatment stations may beof the same or of different types. For example, in some embodiments,contactless treatment stations 614, 616, and 618 may be a contactlessmixer, such as an orbital shaker. In some embodiments, contactlesstreatment stations 620, 622, and 624 may be a contactless heater orincubator. In some embodiments one or more of the contactless treatmentstations may be or include magnet stations for separation of magneticbeads. In some embodiments, contactless treatment stations 614, 616,618, 620, 622, and 624 are operated in parallel, simultaneouslyprocessing multiple sample processing plates.

FIG. 7 is a flowchart of one embodiment of a control system dynamicallyselecting a contactless treatment station for a sample processing platebeing processed by a high-throughput sample processing system with aplurality of different types of contactless treatment stations. At step710, the control system determines the type of contactless treatmentstation is to be used to process a sample processing plate. For example,in some embodiments, the control system determines a contactless mixingstation will process the sample processing plate. In some embodiments,the control system determines a contactless heating station will processthe sample processing plate. In some embodiments, the control systemdetermines a contactless cooling station will process the sampleprocessing plate. In some embodiments, the control system determines acontactless heating-mixing station will process the sample processingplate. In some embodiments, the control system determines a contactlesscooling-mixing station will process the sample processing plate.

At step 720, the control system will determine if a first contactlesstreatment station of the selected type is available to treat a sampleprocessing plate. If the first contactless treatment station of theselected type is available (that is, it is not processing a differentsample processing plate at the time the control system makes thedetermination), then the control system will activate a mechanism fortransporting the sample processing plate to the first contactlesstreatment station of the selected type, for example by activating arobotic arm, sled, drawer, or belt. If the first contactless treatmentstation of the selected type is not available (that is, it is processinga different sample processing plat at the time the control system makesthe determination), then, in some embodiments, the control system willproceed to step 730.

In some embodiments, at step 730, the control system will determine if asecond contactless treatment station of the selected type is availableto treat a sample processing plate. If the second contactless treatmentstation of the selected type is available, then the control system willactivate a mechanism for transporting the sample processing plate to thesecond contactless treatment station of the selected type. If the secondcontactless treatment station of the selected type is not available,then, in some embodiments, the control system will proceed to step 740.

In some embodiments, at step 740, the control system will determine if athird contactless treatment station of the selected type is available totreat a sample processing plate. If the third contactless treatmentstation of the selected type is available, then the control system willactivate a mechanism for transporting the sample processing plate to thethird contactless treatment station of the selected type.

In some embodiments, if the third contactless treatment station of theselected type is not available (or no contactless treatment stations ofthe selected type is available), then the control system may transferthe sample processing plate to a wait nest at step 750 until a furtherprocessing station is available.

Contactless Liquid Level Sensor System

In some embodiments, a contactless liquid level sensor system comprisesa one or more contactless liquid level sensors. In some embodiments, acontactless liquid level sensor can be used to determine the amount ofliquid in a well of a sample processing plate. In some embodiments, anarray of contactless liquid level sensors may be used in ahigh-throughput sample processing system to simultaneously determine theliquid level of a plurality of wells in a sample processing plate. Insome embodiments, the liquid level is measured as volume of liquidwithin the well, approximate meniscus distance from the sensor,approximate meniscus distance from the top of the well, or approximatemeniscus distance from the bottom of the well. In some embodiments,knowledge of the liquid level within a well is important for systemmonitoring, to ensure the contactless fluid dispensing system isdispensing the desired fluid volume and the contactless aspiratingsystem is aspirating the desired fluid volume. This can help minimizewell overflow and ensure consistency.

The liquid level can be determined in a variety of ways, for example,using weight, digital imaging, ultrasonic, or a laser level transmitter.In some embodiments, the liquid levels are measured using sonar oracoustic waves, for example ultrasonic sound waves. FIG. 8 illustratesone embodiment of a single sensor of a contactless liquid level sensor.A sensor 800 comprises a speaker 810, configured to transmit ultrasonicwaves, and a microphone 820, configured to receive ultrasonic waves. Theultrasonic waves transmitted by the speaker 810 can reflect off a samplemeniscus 830 and be received by the microphone 820. In some embodiments,the signals are transmitted to an amplifier. The liquid level of thesample well can be determined by the difference between the transmissionand receiving time of the ultrasonic waves.

In some embodiments, the sensor has a diameter of about the same size asthe diameter of the sample wells. In some embodiments, the sensor has adiameter of about 20 mm or less, about 15 mm or less, about 9 mm orless, about 7 mm or less, or about 5 mm or less, or about 2 mm or less.In some embodiments, the speaker transmits sound waves of about 20 kHzor more, about 50 kHz or more, about 150 kHz or more, about 350 kHz ormore, or about 500 kHz or more. In some embodiments, the sensor has aresolution of about 50 micrometers or less, about 30 micrometers orless, about 20 micrometers or less, about 10 micrometers or less, orabout 5 micrometers or less. In some embodiments, the sensor canaccurately measure the distance of a meniscus less than about 5 mm awayor closer, about 10 mm away or closer, about 25 mm away or closer, about50 mm away or closer, about 100 mm away or closer, about 150 mm away orcloser, or about 250 mm away or closer. In some embodiments, the liquidlevel can be determined in less than about 30 seconds per reading, lessthan about 15 seconds per reading, less than about 10 seconds perreading, less than about 5 seconds per reading, less than about 2seconds per reading, or less than about 1 second per reading.

Contactless Fluid Aspirator

In some embodiments of a high-throughput sample processing system, acontactless fluid aspirator can be used to aspirate fluids from theplurality of wells of the sample processing plate. In some embodiments,a contactless fluid aspirator comprises one or more aspirating nozzlesand a waste conduit fluidly connected to a waste management system. Insome embodiments, a contactless fluid aspirator may also comprise adevice for lowering aspirating nozzles, a device for raising a sampleprocessing plate, or a magnetic base. In some embodiments, thecontactless fluid aspirator may be adjoined to a contactless liquidlevel sensor configured to allow the determination of the liquid levelof the sample wells of the sample processing plate before, during, orafter the contactless fluid aspiration step.

In some embodiments, a suction force allows one or more fluid aspiratingnozzles to draw fluid contained within a plurality of wells of a sampleprocessing plate. In some embodiments, a vacuum, blower, or wastemanagement system may provide the suction force. In some embodiments,the suction force is less than about −10 mmHg relative to ambient, lessthan about −15 mmHg relative to ambient, less than about −20 mmHgrelative to ambient, or less than about −30 mmHg relative to ambient. Insome embodiments the fluid travels through a waste management conduit toa waste management system, where it can be treated and disposed. In someembodiments, the suction force is strong enough to pull liquid from themeniscus of the sample without making contact with any retained sample.In some embodiments, the fluid aspirating nozzles are lowered into thesample wells by a device to maintain an approximately equal distancefrom the tip of the fluid aspirating nozzles and the meniscus of theplurality of samples. In some embodiments, the sample processing plateis raised towards stationary fluid aspirating nozzles by a device tomaintain an approximately equal distance from the tip of the fluidaspirating nozzles and the meniscus of the plurality of samples.

In some embodiments, such as when magnetic affinity beads are used tobind target molecules, the sample processing plate may sit upon amagnetic base. The magnetic base forces the magnetic affinity beads tothe bottom of the sample wells, thereby avoiding the suction force ofthe fluid aspiration nozzles. This substantially prevents sample lossduring the contactless fluid aspiration step, as it decreases thelikelihood affinity beads will be unintentionally aspirated from thesample wells.

In some embodiments, the contactless fluid aspirator comprise a barcodescanner, which can scan a barcode provided by the sample processingplate and transmit the location of an individual sample processing plateto a control system.

FIG. 9 illustrates one embodiment of a contactless fluid aspirator. Thesample processing plate 902 is placed on an aspirating tray 904. In someembodiments, the aspirating tray 904 is used to transport the sampleprocessing plate 902 between one or more components of thehigh-throughput sample processing system. In some embodiments, thesample processing plate 902 is placed on the aspirating tray 904 onlyduring operation of the contactless fluid aspirator. In someembodiments, the aspirating tray 904 comprises magnets. In someembodiments, the aspirating tray 904 magnet provides a magnetic force toretain magnetic beads disposed within the plurality wells of the sampleprocessing plate 902 during fluid aspiration. In some embodiments, thishelps prevent sample loss or affinity bead loss during fluid aspiration.

In some embodiments, the contactless fluid aspirator comprises aplurality of aspirating nozzles 906. In some embodiments, thecontactless fluid aspirator comprises as many aspirating nozzles 906 asthere are sample wells in the sample processing plate 902. In someembodiments, the contactless fluid aspirator comprises fewer aspiratingnozzles 906 than the number of sample wells in the sample processingplate 902. In some embodiments, the contactless fluid aspiratorcomprises as many aspirating nozzles 906 as there are wells in a singlecolumn or single row of the sample processing plate 902. In someembodiments, the aspirating nozzles are fluidly connected to a nozzlearray 908.

In some embodiments, an aspirating waste conduit 910 fluidly links thenozzle array 908 with a vacuum source 912, for example a wastemanagement system. In some embodiments, the vacuum source 912 provides apressure gradient, allowing liquid to flow through the aspiratingnozzles 906, nozzle array 908, and aspirating waste conduit 910. In someembodiments, the vacuum source 912 provides a sufficiently strong vacuumsuch that the aspirating nozzles 906 can siphon fluid from a sample wellin the sample processing plate 902 without traversing the samplemeniscus.

In some embodiments, the aspirating nozzles 906 maintain a distance fromthe sample meniscus such that fluid is continuously aspirated from thesample until a predetermined amount of fluid is aspirated. In someembodiments, the aspirating nozzles 906 are lowered into the samplewells of the sample processing plate 902 to maintain an appropriatedistance from the sample meniscus as fluid is being aspirated. In someembodiments, the sample processing plate 902 is raised (for example byraising the aspirating tray 904) to maintain an appropriate distancebetween the sample meniscus and the aspirating nozzles 906 as fluid isbeing aspirated.

Waste Management System

In some embodiments, liquid waste from the high-throughput sampleprocessing system is transported to a waste management system via one ormore waste conduits, where it can be treated and disposed. In someembodiments, the waste conduits comprise a corrosive-resistant material,such as polytetrafluoroethylene. In some embodiments, liquid waste maybe produced from washing pipette tips in the sample dispensing device,aspirated fluid from the contactless fluid aspirator, any spilled fluidduring sample processing that may arise, for example overflowing of thesample processing plate wells, or fluid from priming of a pump. In someembodiments, a waste management system can treat and dispose of morethan about 10 liters of liquid waste per day, more than about 20 litersof liquid waste per day, more than about 40 liters of liquid waste perday, more than about 60 liters of liquid waste per day, more than 100liters of liquid per day, more than 200 liters of liquid per day, morethan 500 liters of liquid per day, or more than 1000 liters of liquidper day.

FIG. 10 illustrates one embodiment of a waste management system 1000that may be used with a high-throughput sample processing system. Insome embodiments, waste may be collected by the waste management system1000 using gravity or suction forces. In some embodiments, liquid wastefrom the contactless fluid aspirator 1002 flows into the wastemanagement system 1000 using a suction force provided by suction source1004, such as a vacuum or blower. In some embodiments, the suctionsource 1004 provides a pressure of less than about −10 mmHg relative toambient, less than about −15 mmHg relative to ambient, less than about−20 mmHg relative to ambient, or less than about −30 mmHg relative toambient. In some embodiments, liquid waste from a sample dispensingdevice 1006 or a waste overflow drainage tray 1008 can flow into agravity waste collection container 1010. In some embodiments a valve1012 can be opened by a control system to allow liquid waste to flowfrom the gravity waste collection container 1010 to the other componentsof the waste management system 1000 under suction forces. Preferably,during normal operation of the high-throughput sample processing system,valve 1012 remains closed to provide optimal suction forces for thecontactless fluid aspirator 1002, opening as necessary to empty thegravity waste collection container 1010.

In some embodiments, liquid waste from the high-throughput sampleprocessing system flows into either a first liquid waste tank 1014 or asecond liquid waste tank 1016. In some embodiments, the waste managementsystem 1000 may have more than two liquid waste tanks, while in otherembodiments the waste management system 1000 may have only one liquidwaste tank. A first flow valve 1018 and a second flow valve 1020 arealternatively opened (such that the first flow valve 1018 is opened whenthe second flow valve 1020 is closed and the first flow valve 1018 isclosed when the second flow valve 1020 is opened), allowing liquid wasteto flow into only one liquid waste tank at any given time. In someembodiments, the first liquid waste tank 1014 and second liquid wastetank 1016 are fluidly connected to an overflow tank 1022, which isfluidly connected to the suction source 1004. In some embodiments, afirst overflow valve 1024 separates the first liquid waste tank 1014from the overflow tank 1022 and a second overflow valve 1026 separatesthe second liquid waste tank 1016 from the overflow tank 1022. The firstoverflow valve 1024 is configured to be open when the first flow valve1018 is opened and closed when the first flow valve 1018 is closed.Similarly, the second overflow valve 1026 is configured to be open whenthe second flow valve 1020 is opened and closed when the second flowvalve 1020 is closed. This configuration allows the suction forcegenerated by the suction source 1004 to pull liquid waste into theliquid waste tanks 1014 or 1016 and, in the event of overflow, into theoverflow tank 1022. In some embodiments, release valves 1028 and 1030can be disposed on the first liquid waste tank 1014 and the secondliquid waste tank 1016, and can be configured to open if, for example,the liquid waste tank overflows or the pressure drops blow apredetermined pressure. The overflow tank can also be used, for example,as a vacuum ballast to maintain the vacuum in the waste system duringoperation. In some embodiments, the release valves 1028 and 1030 arecontrolled by the control system.

In some embodiments, a sterilizing solution tank 1032 comprises asterilizing solution, for example bleach, hydrogen peroxide, or iodinesolution, and is fluidly connected to the first liquid waste tank 1014and the second liquid waste tank 1016. Once a liquid waste tank 1014 or1016 is at a predetermined capacity, the flow valve 1018 or 1020 and theoverflow valve 1026 or 1026 can be turned off and a sterilizing solutionvalve 1034 or 1036 can be opened. A sterilizing solution pump 1038 canpump an appropriate amount of sterilizing solution from the sterilizingsolution tank 1032 into the liquid waste tank 1014 or 1016. In someembodiments the amount of sterilizing solution pumped into the liquidwaste tanks 1014 or 1016 is determined by the control system afterdetermining the weight of liquid waste in the liquid waste tanks 1014 or1016. In some embodiments, the amount of liquid in any tank, includingthe liquid waste tank 1014 or 1016, the gravity waste collectioncontainer 1010, the overflow tank 1022, or the sterilizing solution tank1032 may be determined. A variety of sensors may be used to determinethe amount of fluids in the waste management system. The sensors mayinclude, for example, acoustic sensors, weight sensors, pressure sensorsetc. In some embodiments, scales can be used to determine how much fluidhas flowed from the high-throughput sample processing system into thewaste management system 1000. In some embodiments, the scales candetermine how much fluid was aspirated from the plurality of wells in asample processing plate by the contactless fluid aspirator that flowedto a liquid waste container 1014 or 1016. Scales are useful fordetermining the amount of fluids removed under vacuum. In someembodiments, the amount of fluid traveling through the system ismonitored, for example, to determine whether there is a leak or error inthe system. Scales and/or other sensors may be used for wastes andliquids in the waste management system that are not under valcuum, e.g.,acoustic, pressure.

A series of valves may be included to ensure the proper operation ofvacuum. In some embodiments the waste is removed using gravity. In someembodiments, the waste management system mixes the fluids removed fromthe plurality of wells with bleach in the waste container and incubatesthe mixture. In some embodiments, the waste management system comprisesone or more sensors for determining an amount of fluids removed from theplurality of wells. These sensors may include, for example, acousticsensors, weight sensors, pressure sensors etc. In some embodiments, thewaste management system comprises one or more scales for determining anamount of fluids removed from the plurality of wells using a vacuum.

In some embodiments, after the sterilizing solution has been injectedinto the liquid waste tank 1014 or 1016, the liquid waste is incubatedfor a predetermined period of time, allowing the neutralization of anybiohazardous material. In some embodiments, the liquid waste incubatesfor 5 minutes or more, 15 minutes or more, 30 minutes or more, 60minutes or more, or 120 minutes or more, or 180 minutes or more. Afterincubation of the liquid waste, a drainage valve 1040 or 1042 is opened,allowing the waste to drain from the waste management system 1000 intoan appropriate location, for example a holding tank or sewage system1044. In some embodiments, release valves 1028 or 1030 may be opened ordrainage pump 1046 can pump liquid from the liquid waste tanks 1014 or1016 to accelerate expulsion of the liquid. In some embodiments, thetreated liquid waste is disposed of in sewage pipes.

In some embodiments, a control system monitors volumes of the liquidwaste tank 1014 or 1016, the gravity waste collection container 1010,the overflow tank 1022, or the sterilizing solution tank 1032. In someembodiments, a control system monitors flow levels of the sterilizingsolution pump 1038 or the drainage pump 1046. In some embodiments, thecontrol system monitors pressures within the waste management system1000. In some embodiments, if any volume, pump flow level, or pressureis above a predetermined value or below a predetermined value, thecontrol system may signal an alarm or terminate the high-throughputsample processing system operation.

By including a waste management system, a high-throughput sampleprocessing system can continuously process and dispose of liquid wasteresulting from system use. The waste management system increases workersafety, as there is decreased likelihood of contact with the liquidwaste. Furthermore, allowing the waste to be continuously treated anddisposed of decreases the expense of liquid waste collection andoff-site disposal, providing a more cost-effective system thanpreviously known sample treatment methods and to allow for unattendedoperation of the system.

EXEMPLARY EMBODIMENTS

The invention is further described by the following embodiments.

Embodiment 1

In one embodiment a high throughput sample processing system comprises:a sample dispensing device for drawing a plurality of samples from aplurality of sample containers and for dispensing each sample into awell of a sample processing plate comprising a plurality of wells,wherein each sample is dispensed into a different well; a fluiddispensing device for dispensing fluids into the plurality of wells ofthe sample processing plate; a plurality of liquid level sensors fordetecting the liquid level in each of the plurality of wells of thesample processing plate; a plurality of aspirators for removing fluidsfrom the plurality of wells of the sample processing plate; a pluralityof treatment stations for treating a plurality of sample processingplates simultaneously; a waste management system for managing fluidsremoved from the plurality of wells; and a control system forcontrolling the processing of a plurality of plates within the highthroughput sample processing system simultaneously.

Embodiment 2

In a further embodiment of embodiment 1 or any exemplarily embodimentherein, the control system dynamically controls the processing of aplate depending upon the location or status of other plates in thesystem.

Embodiment 3

In a further embodiment of embodiment 1, 2 or any exemplarily embodimentherein, the high throughput sample processing system comprises one ormore magnetic stations.

Embodiment 4

In a further embodiment of embodiment 1-3 or any exemplarily embodimentherein, the fluid dispensing device is contactless.

Embodiment 5

In a further embodiment of embodiment 1-4 or any exemplarily embodimentherein, the liquid level sensors are contactless.

Embodiment 6

In a further embodiment of embodiment 1-5 or any exemplarily embodimentherein, the treatment stations are contactless.

Embodiment 7

In a further embodiment of embodiment 1-6 or any exemplarily embodimentherein, the high throughput sample comprises a plate loading device forautomatically loading additional plates into the sample dispensingdevice.

Embodiment 8

In a further embodiment of embodiment 1-7 or any exemplarily embodimentherein, the samples comprise blood, saliva, and/or plasma.

Embodiment 9

In a further embodiment of embodiment 1-8 or any exemplarily embodimentherein, the high throughput system extracts DNA from the plurality ofsamples using magnetic beads.

Embodiment 10

In a further embodiment of embodiment 1-9 or any exemplarily embodimentherein, the sample dispensing device comprises a plurality of syringebased pipettes.

Embodiment 11

In a further embodiment of embodiment 1-10 or any exemplarily embodimentherein, the sample dispensing device comprises a plurality of reusablesyringe based pipettes.

Embodiment 12

In a further embodiment of embodiment 10, 11 or any exemplarilyembodiment herein, the sample dispensing device comprises a washingstation for automatically washing the reusable pipette tips.

Embodiment 13

In a further embodiment of embodiment 12 or any exemplarily embodimentherein, the washing station comprises a bleach solution.

Embodiment 14

In a further embodiment of embodiment 1-13 or any exemplarily embodimentherein, the sample containers are sealed and pipettes are configured todraw the plurality of samples through seals of the containers.

Embodiment 15

In a further embodiment of embodiment 1-14 or any exemplarily embodimentherein, the liquid level sensors comprise one or more acoustic sensors.

Embodiment 16

In a further embodiment of embodiment 1-15 or any exemplarily embodimentherein, the waste management system deposits the fluids removed from theplurality of wells into a waste container.

Embodiment 17

In a further embodiment of embodiment 16 or any exemplarily embodimentherein, the waste container operates under a vacuum.

Embodiment 18

In a further embodiment of embodiment 1-17 or any exemplarily embodimentherein, the waste management system mixes the fluids removed from theplurality of wells with bleach in the waste container and incubates themixture.

Embodiment 19

In a further embodiment of embodiment 1-18 or any exemplarily embodimentherein, the waste management system comprises one or more scales fordetermining an amount of fluids removed from the plurality of wells.

Embodiment 20

In a further embodiment of embodiment 1-19 or any exemplarily embodimentherein, the plurality of treatment stations comprise one or more mixingdevices.

Embodiment 21

In a further embodiment of embodiment 20 or any exemplarily embodimentherein, the one or more mixing devices comprises one or more orbitalshakers.

Embodiment 22

In a further embodiment of embodiment 1-21 or any exemplarily embodimentherein, the plurality of treatment stations comprise one or more heatingor cooling devices.

Embodiment 23

In a further embodiment of embodiment 1-22 or any exemplarily embodimentherein, the high throughput sample processing system comprises a barcodescanner for identifying samples using barcodes on the sample containers.

Embodiment 24

In one embodiment a high throughput sample processing method comprises:drawing a plurality of samples from a plurality of sample containers;dispensing each sample into a well of a sample processing platecomprising a plurality of wells, wherein each sample is dispensed into adifferent well; dispensing fluids into the plurality of wells of thesample processing plate using a contactless fluid dispensing device;detecting the liquid level in each of the plurality of wells of thesample processing plate using a plurality of contactless liquid levelsensors; mixing a plurality of sample processing plates simultaneouslyusing a plurality of contactless mixing devices; removing fluids fromthe plurality of wells of the sample processing plate using a pluralityof aspirators; and managing fluids removed from the plurality of wellsusing a waste management system.

Embodiment 25

In a further embodiment of embodiment 24 or any exemplarily embodimentherein, comprising dynamically controlling the processing of a platedepending upon the location or status of other plates.

Embodiment 26

In a further embodiment of embodiment 24, 25, or any exemplarilyembodiment herein, further comprising automatically loading additionalplates into the sample dispensing device.

Embodiment 27

In a further embodiment of embodiment 24-26 or any exemplarilyembodiment herein, the plurality of samples comprise blood, plasma orsaliva.

Embodiment 28

In a further embodiment of embodiment 24-27 or any exemplarilyembodiment herein, the method comprises extraction of DNA from theplurality of samples using magnetic beads.

Embodiment 29

In a further embodiment of embodiment 24-28 or any exemplarilyembodiment herein, the samples are dispensed using a plurality ofsyringe based pipettes.

Embodiment 30

In a further embodiment of embodiment 29 or any exemplarily embodimentherein, the pipettes comprise reusable pipette tips.

Embodiment 31

In a further embodiment of embodiment 29-30 or any exemplarilyembodiment herein, further comprising automatically washing the reusablepipette tips.

Embodiment 32

In a further embodiment of embodiment 29-31 or any exemplarilyembodiment herein, the pipette tips are automatically washed using ableach solution.

Embodiment 33

In a further embodiment of embodiment 24-31 or any exemplarilyembodiment herein, the liquid level sensors comprise one or moreacoustic sensors.

Embodiment 34

In a further embodiment of embodiment 24-33 or any exemplarilyembodiment herein, the waste management system deposits the fluidsremoved from the plurality of wells into a waste container.

Embodiment 35

In a further embodiment of embodiment 24-34 or any exemplarilyembodiment herein, the waste container operates under a vacuum.

Embodiment 36

In a further embodiment of embodiment 24-35 or any exemplarilyembodiment herein, the waste management system mixes the fluids removedfrom the plurality of wells with bleach in the waste container andincubates the mixture.

Embodiment 37

In a further embodiment of embodiment 24-36 or any exemplarilyembodiment herein, the waste management system comprises one or morescales for determining an amount of fluids removed from the plurality ofwells.

Embodiment 38

In a further embodiment of embodiment 24-37 or any exemplarilyembodiment herein, the plurality of contactless mixing devices comprisesone or more orbital shakers.

Embodiment 39

In a further embodiment of embodiment 24-38 or any exemplarilyembodiment herein, comprising scanning a barcode scanner on the samplecontainers to identify the samples.

Embodiment 40

An embodiment of a non-transitory computer-readable storage medium foroperating a high throughput sample processing system, thecomputer-readable storage medium comprising instructions for:dynamically scheduling multiple sample processing plates for processingthrough a sample processing system, wherein the scheduling depends uponthe location or status of other sample processing plates in the sampleprocessing system; controlling one or more robotic mechanisms fortransferring sample processing plates among devices within the sampleprocessing system according to the dynamic scheduling; operating asample dispensing device operable for drawing a plurality of samplesfrom a plurality of sample containers and for dispensing each sampleinto a well of a sample processing plate comprising a plurality ofwells, wherein each sample is dispensed into a different well; operatinga contactless fluid dispensing device operable for dispensing fluidsinto the plurality of wells of each of the sample processing plates;operating a plurality of contactless liquid level sensors operable fordetecting the liquid level in each of the plurality of wells of each ofthe sample processing plates; operating a plurality of aspirators forremoving fluids from the plurality of wells of each of the sampleprocessing plates; operating a plurality of contactless mixing devicesfor mixing a plurality of sample processing plates simultaneously; andoperating a waste management system for managing fluids removed from theplurality of wells.

Embodiment 41

In a further embodiment of embodiment 40 or any exemplarily embodimentherein, the plurality of samples comprise blood, plasma or saliva.

Embodiment 42

In a further embodiment of embodiment 40-41 or any exemplarilyembodiment herein, wherein the instructions comprises instructions forextraction of DNA from the plurality of samples using magnetic beads.

Embodiment 43

In a further embodiment of embodiment 40-42 or any exemplarilyembodiment herein, the samples are dispensed using a plurality ofsyringe based pipettes.

Embodiment 44

In a further embodiment of embodiment 43 or any exemplarily embodimentherein, the pipettes comprise reusable pipette tips.

Embodiment 45

In a further embodiment of embodiment 43-44 or any exemplarilyembodiment herein, further comprising automatically washing the reusablepipette tips.

Embodiment 46

In a further embodiment of embodiment 43-45 or any exemplarilyembodiment herein, the pipette tips are automatically washed using ableach solution.

Embodiment 47

In a further embodiment of embodiment 24-31 or any exemplarilyembodiment herein, the liquid level sensors comprise one or moreacoustic sensors.

Embodiment 48

In a further embodiment of embodiment 40-47 or any exemplarilyembodiment herein, the waste management system deposits the fluidsremoved from the plurality of wells into a waste container.

Embodiment 49

In a further embodiment of embodiment 40-48 or any exemplarilyembodiment herein, the waste container operates under a vacuum.

Embodiment 50

In a further embodiment of embodiment 40-49 or any exemplarilyembodiment herein, the waste management system mixes the fluids removedfrom the plurality of wells with bleach in the waste container andincubates the mixture.

Embodiment 51

In a further embodiment of embodiment 40-50 or any exemplarilyembodiment herein, the waste management system comprises one or morescales for determining an amount of fluids removed from the plurality ofwells.

Embodiment 52

In a further embodiment of embodiment 40-51 or any exemplarilyembodiment herein, the plurality of contactless mixing devices comprisesone or more orbital shakers.

Embodiment 53

In a further embodiment of embodiment 40-52 or any exemplarilyembodiment herein, wherein the instructions comprises instructions forscanning a barcode scanner on the sample containers to identify thesamples.

Embodiment 54

An embodiment of a waste management system for processing waste producedby a high-throughput sample processing system, comprises: agravity-based liquid waste input; a vacuum-based liquid waste input; asterilizing fluid container; two or more liquid waste containers,configured to alternatively accept liquid waste, treat the liquid wastewith a sterilizing fluid, and incubate the sterilizing fluid in theliquid waste for a predetermined period of time before disposing of thetreated liquid waste; and one or more scales for determining the amountof liquid waste collected by the one or more liquid waste containers.

Embodiment 55

In a further embodiment of embodiment 54 or any exemplarily embodimentherein, the sterilization fluid comprises bleach.

This application discloses several numerical ranges in the text andfigures. The numerical ranges disclosed inherently support any range orvalue within the disclosed numerical ranges even though a precise rangelimitation is not stated verbatim in the specification because thisinvention can be practiced throughout the disclosed numerical ranges.

The above description is presented to enable a person skilled in the artto make and use the invention, and is provided in the context of aparticular application and its requirements. Various modifications tothe preferred embodiments will be readily apparent to those skilled inthe art, and the generic principles defined herein may be applied toother embodiments and applications without departing from the spirit andscope of the invention. Thus, this invention is not intended to belimited to the embodiments shown, but is to be accorded the widest scopeconsistent with the principles and features disclosed herein. Finally,the entire disclosure of the patents and publications referred in thisapplication are hereby incorporated herein by reference.

What is claimed is:
 1. A waste management system for processing wasteproduced by a high-throughput sample processing system, comprising: afirst pump; a second pump; a first valve; a second valve; a third valve;a fourth valve; a controller communicatively coupled to thehigh-throughput waste management system and programmed to control thefirst pump, the second pump, the first valve, the second valve, thethird valve and the fourth valve; a first container fluidly connected tothe first pump via the first and second valves, wherein first liquidwaste moves from a first liquid waste source to the first container viaa suction force provided by the first pump when the controller opens thefirst and second valves; a second container fluidly connected to thefirst pump via the first, second, and third valves, wherein secondliquid waste moves from a second liquid waste source to the secondcontainer via gravity, and wherein the second liquid waste moves fromthe second container to the first container via the suction forceprovided by the first pump when the controller opens the first, second,and third valves; a third container that holds a sterilizing fluid andis fluidly connected to the first container via the fourth valve;wherein the second pump pumps the sterilizing fluid into the firstcontainer when the controller opens the fourth valve, and wherein thefirst container is configured to treat the liquid waste therein with thesterilizing fluid, and to incubate the treated liquid waste in thesterilizing fluid for a predetermined period of time before disposing ofthe treated liquid waste when directed by the controller.
 2. The wastemanagement system of claim 1, further comprising: a sample processingplate comprising a plurality of sample wells; and a plurality of fluidaspirators connected to the first pump and operable to draw the firstliquid waste into the first container from the sample wells.
 3. Thewaste management system of claim 1, further comprising: a scale operableto measure at least one of the first and second liquid wastes.
 4. Thewaste management system of claim 1, further comprising: a fourthcontainer connected to the first and second containers and operable toreceive overflow liquid waste from at least one of the first and secondcontainers.
 5. The waste management system of claim 1, furthercomprising: a third pump operable to pump the first and second treatedliquid wastes into a drainage system.
 6. The waste management system ofclaim 1, further comprising: a control system operable to determine anamount of the sterilizing fluid that is to be pumped into the first andsecond containers.